Antibody-based immunotherapy holds promise as an important strategy for the prevention and treatment of HIV infection. This treatment modality may be effective as a monotherapy or might be used to augment current regimens that target different steps in the HIV replication cycle. Critical to identifying and evaluating such therapies will be the development of relevant animal models in which new immunotherapies can be tested. The nonhuman primate models of AIDS have been extremely useful for clarifying mechanisms of disease pathogenesis, for evaluating new HIV vaccine strategies and testing therapies. The recent development of chimeric simian/human immunodeficiency viruses (SHIVs) has greatly enhanced the utility of these animal models. Certain chimeric viruses that express HIV-1 envelopes on SIV backbones (SHIVs) infect and cause AIDS in rhesus monkeys. This new SHIV/rhesus monkey model will be a powerful tool for testing the utility of envelope-directed therapies. Immunotherapies that target certain cell surface molecules, such as the HIV receptor molecules, may represent an alternative approach to treating AIDS. In fact, preliminary data indicates that certain anti-CD4 monoclonal antibodies may be effective in preventing and treating HIV infection. In the experiments described in this proposal, the investigaotrs will: I. Develop the rhesus monkey infected with a chimeric simian/human immunodeficiency virus (SHIV) as an animal model for evaluating passive immunotherapy for the prevention and treatment of HIV infection. II. Utilize this model to evaluate a unique, humanized anti-CD4 antibody as an anti-viral therapy for the treatment and prevention of HIV infection.